[Inhibitory effect of IGF1R siRNA on the growth of human liver cancer SMMC7721 cell xenograft in nude mice]

Abstract

Background & objective: Using small interfering RNA (siRNA) to inhibit mammal gene expression becomes an effective technique in studying gene function. This study was to investigate the effect of insulin-like growth factor 1 receptor (IGF1R) siRNA on the growth of human liver cancer SMMC7721 cell xenograft in nude mice.

Methods: siRNA targeting IGF1R was designed, and plasmid SMMC7721-IGF1R-siRNA was constructed and transfected into SMMC7721 cells (SMMC7721-IGF1R-siRNA cells); the cells transfected with SMMC7721-IGF1R-mutation (SMMC7721-IGF1R-mutation cells) were used as negative control, and untransfected cells as empty control. Stable cell clones were screened by G418, and transplanted into nude mice to establish cancer xenograft. Tumor growth was monitored. Tumor morphology was observed with HE staining. The expression of IGF1R protein in tumor tissues was detected by Western blot. Microvessel density (MVD) in tumor tissues was detected by SP immunohistochemistry. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay.

Results: The tumor volume was significantly smaller in SMMC7721-IGF1R-siRNA group than in SMMC7721-IGF1R-mutation group and SMMC7721 group (P < 0.05). Necrosis and cell apoptosis were found in SMMC7721-IGF1R-siRNA group. The expression of IGF1R protein was significantly lower in SMMC7721-IGF1R-siRNA group than in SMMC7721-IGF1R-mutation group and SMMC7721 group (P < 0.05). MVD was significantly lower in SMMC7721-IGF1R-siRNA group than in SMMC7721-IGF1R-mutation group and SMMC7721 group (11.3+/-4.4 vs. 36.7+/-7.6 and 28.4+/-6.5, P < 0.05). The apoptosis rate of tumor cells was significantly higher in SMMC7721-IGF1R-siRNA group than in SMMC7721-IGF1R-mutation group and SMMC7721 group [(50.2+/-6.4)% vs. (5.4+/-1.0)% or (6.0+/-2.1)%, P < 0.05].

Conclusion: IGF1R siRNA can inhibit the growth of SMMC7721 cell xenograft in nude mice.